Safety of reduced antigen content diphtheria-tetanus-acellular pertussis vaccine when administered during pregnancy as part of the maternal immunization program in Brazil: a single center, observational, retrospective, cohort study

ABSTRACT

Reduced antigen diphtheria-tetanus-acellular pertussis (Tdap) vaccination is included in the maternal immunization program in Brazil since September 2014. We investigated associations between maternal Tdap vaccination and pregnancy-related adverse events (AEs) (gestational diabetes, pregnancy-related hypertension, and pregnancy hemorrhage) and neonatal AEs of interest (preterm birth and small for gestational age). This descriptive, observational, retrospective, single-center study in Brazil (NCT02757950) compared data from medical charts of 1203 pregnant women who received Tdap as part of the maternal immunization program and delivered between May 2015 and February 2017 (exposed cohort) and 1259 unvaccinated women who delivered between September 2012 and August 2014 (unexposed cohort). Index dates were defined as the time of vaccination (27–39 gestational weeks; exposed cohort) or 27 gestational weeks (unexposed cohort). Cumulative incidences were calculated as the number of women with each event between index and delivery dates divided by the total number of women with vaccination date available in the exposed cohort (N = 1199) or the total number of women in the unexposed cohort (N = 1259). Cumulative incidences per 1000 persons were 8.34 versus 17.47 for gestational diabetes, 9.17 versus 24.62 for pregnancy-related hypertension, 3.34 versus 15.09 for pregnancy hemorrhage, 53.38 versus 96.11 for preterm birth, and 57.55 versus 49.25 for small for gestational age in the exposed versus unexposed cohorts. No increased risk of pregnancy-related AEs or neonatal AEs of interest was found following maternal vaccination with Tdap. These results should be interpreted cautiously due to limitations inherent to retrospective observational studies.

KEYWORDS:

• Pertussis
• maternal vaccination
• adverse event
• pregnancy
• neonate

Trademark statement

Refortrix and Boostrix trademarks are owned by the GSK group of companies. Refortrix is a trademark specific to Brazil.

Abbreviations

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Acknowledgments

The authors would like to thank all study participants, especially the direction of the Hospital Municipal Universitário de São Bernardo, the staff of the Research Center of the Faculty of Medicine of ABC, and the nurses Margarete F C Carvalho and Alice Carlotta. We would also like to thank Ariane Abreu (Shift Gestão de Serviços working for GSK Vaccines Brazil) for her support on the data cleaning, Rodrigo DeAntonio-Suarez (GSK Vaccines LATAM) for his supervision and appreciated inputs during the study development, Susana Soares and Andreia Neves, and the Brazilian Clinical Operations team for their strong dedication for the study implementation, and Miguel Vicco for his contribution to the data interpretation. The authors would also like to thank XPE Pharma & Science platform for editorial assistance and manuscript coordination on behalf of GSK: Claire Verbelen (XPE Pharma and Science) provided medical writing support and Iudit-Hajnal Filip and Michaela Conrad coordinated manuscript development and provided editorial support.

Authors’ Contributions

DL, EdB, MS, and YF were involved in study conception and design. DL, EdB, MS, NM, and YF performed the study, participated or collected the data. DL, EdB, AC, NM, and YF were involved in data analysis and interpretation. EdB participated in the feasibility assessment and selection of the study site. EdB and DL were involved in the study oversight (DL for central study oversight, EdB for local study oversight). All authors have drafted or reviewed the manuscript, they have all approved the final version of the manuscript as submitted and all accept full accountability for the content.

Disclosure of potential conflicts of interest

DL, EdB, AC, and NM are employed by the GSK group of companies. EdB, DL and NM hold shares in the GSK group of companies. YF works as external consultant declaring personal fees from the GSK group of companies for performing the statistical analysis of the study. MS has no potential conflict of interest to disclose.

Supplementary material

Supplemental data for this article can be accessed on publisher’s website.

Additional information

Funding

This study and related publication were supported by GlaxoSmithKline Biologicals S.A.